The objectives of this project are to study the nature of the complex saccharides (acid polysaccharides, glycoproteins, glycolipids) associated with the nuclei of normal and cancerous mammalian cells; their localization in the nucleus and their biological function with special emphasis on possible alterations in oncogenic cells. Normal and virus transformed (e.g., Herpes simplex, SV40, cytomegalo, hamster sarcoma) fibroblasts, B16 mouse melanoma, human melanoma, rat liver cells and rat hepatoma cultured cells will be employed for this purpose. Solid tumors (e.g., melanoma, hepatoma) will also be utilized when preparative quantities of specific products are desired. Nuclei will be isolated from cells labeled with (3H)glucosamine and 35 SO4-- and the complex saccharides solubilized by treatment with proteolytic enzymes or with detergents. The acidic polysaccharides and glycoproteins will be separated from each other by precipitation with quaternary ammonium salts. After further fractionation by chromatography (gel filtration, ion exchange) the components will be characterized by chemical and enzymatic methods. Localization of these components in the nucleus will be attempted by examination of the nuclei and nuclear membrane by electron microscopy and autoradiography. The biological functions of these polymers in the nuclei will be investigated by determining their qualitative and quantitative changes during the cell cycle, as a function of cell density and as a consequence of malignancy. In addition, the influence of exogenously added or removal of endogenous complex saccharides on the in vitro DNA and RNA synthesis and on the ion binding properties of the nuclei will also be determined. These studies constitute a new approach to understanding the uncontrolled growth of cancer cells by examining the role of endogenous nuclear mucopolysaccharides in the initiation and control of cell division.